E. Mitrová (Eva)http://repub.eur.nl/ppl/11013/
List of Publicationsenhttp://repub.eur.nl/eur_signature.pnghttp://repub.eur.nl/
RePub, Erasmus University RepositoryCathepsin D (C224T) polymorphism in sporadic and genetic creutzfeldt-jakob diseasehttp://repub.eur.nl/pub/28062/
Fri, 01 Jan 2010 00:00:01 GMT<div>G.G. Kovacs</div><div>P. Sanchez-Juan</div><div>T. Ströbel</div><div>M. Schuur</div><div>A. Poleggi</div><div>S. Nocentini</div><div>C. Giannattasio</div><div>G. Belay</div><div>M. Bishop</div><div>S. Capellari</div><div>P. Parchi</div><div>E. Gelpi</div><div>A. Gal</div><div>A. Bakos</div><div>M.J. Molnar</div><div>U. Heinemann</div><div>I. Zerr</div><div>R.S.G. Knight</div><div>E. Mitrová</div><div>P. Tikka-Kleemola</div><div>H. Budka</div>
Accumulation of cathepsin D immunoreactive lysosomes correlates with tissue pathology in sporadic Creutzfeldt-Jakob disease (CJD) brains. The C-to-T transition within exon 2 of the cathepsin D (CTSD) gene is associated with altered enzymatic activity. Possession of the TT genotype is a risk factor for variant CJD. To verify the association between the CTSD position 224T allele and the risk for and survival in sporadic and genetic CJD, we genotyped 540 sporadic, 101 genetic CJD, and 723 control individuals. Genotype data and duration of illness were compared using multiple logistic regression and Kruskal-Wallis test. Multivariate survival analysis was performed using Cox's regression model. The distribution of CTSD position 224 alleles was approximately the same in all groups. We observed a trend for shorter survival in sporadic CJD patients harboring the T allele at position 224 of the CTSD gene in particular in sporadic CJD patients with the prion protein gene position 129 MM genotype. We conclude that the CTSD position 224 polymorphism alone is not a significant risk or disease-modifying factor in sporadic or genetic CJD. Cerebrospinal fluid biomarkers in human genetic transmissible spongiform encephalopathieshttp://repub.eur.nl/pub/17945/
Thu, 01 Oct 2009 00:00:01 GMT<div>A. Ladogana</div><div>P. Sanchez-Juan</div><div>E. Mitrová</div><div>A. Green</div><div>N. Cuadrado-Corrales</div><div>R. Sánchez-Valle</div><div>S. Koscova</div><div>A. Aguzzi</div><div>T. Sklaviadis</div><div>J. Kulczycki</div><div>J. Gawinecka</div><div>A. Saiz</div><div>M. Calero</div><div>C.M. van Duijn</div><div>M. Pocchiari</div><div>R. Knight</div><div>I. Zerr</div>
The 14-3-3 protein test has been shown to support the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) when associated with an adequate clinical context, and a high differential potential for the diagnosis of sporadic CJD has been attributed to other cerebrospinal fluid (CSF) proteins such as tau protein, S100b and neuron specific enolase (NSE). So far there has been only limited information available about biochemical markers in genetic transmissible spongiform encephalopathies (gTSE), although they represent 10-15% of human TSEs. In this study, we analyzed CSF of 174 patients with gTSEs for 14-3-3 (n = 166), tau protein (n = 78), S100b (n = 46) and NSE (n = 50). Levels of brain-derived proteins in CSF varied in different forms of gTSE. Biomarkers were found positive in the majority of gCJD (81%) and insert gTSE (69%), while they were negative in most cases of fatal familial insomnia (13%) and Gerstmann-Sträussler-Scheinker syndrome (10%). Disease duration and codon 129 genotype influence the findings in a different way than in sporadic CJD.Influence of timing on CSF tests value for Creutzfeldt-Jakob disease diagnosishttp://repub.eur.nl/pub/36065/
Sun, 01 Jul 2007 00:00:01 GMT<div>P. Sanchez-Juan</div><div>R. Sánchez-Valle</div><div>A. Green</div><div>A. Ladogana</div><div>N. Cuadrado-Corrales</div><div>E. Mitrová</div><div>K. Stoeck</div><div>T. Sklaviadis</div><div>J. Kulczycki</div><div>K. Hess</div><div>A. Krasnianski</div><div>M. Equestre</div><div>D. Slivarichová</div><div>A. Saiz</div><div>M. Calero</div><div>M. Pocchiari</div><div>R.S.G. Knight</div><div>P. Tikka-Kleemola</div><div>I. Zerr</div>
Background: The analysis of markers in the cerebrospinal fluid (CSF) is useful in the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). However, the time at which the study of these markers is most sensitive remains controversal. Objective: To assess the influence of time of sampling on the value of CSF tests in the diagnosis of sCJD. Method: In the framework of a multinational European study, we studied the results of 14-3-3, S100b, neurone specific enolase (NSE) and tau protein in 833 CSF samples from sCJD patients at different stages of disease and in 66 sequentially repeated lumbar punctures (LP). Results: 14-3-3 and tau protein tended to increase in sensitivity from onset (88%, 81%) to the advanced stage (91%, 90%). This was significant only in the methionine-valine (MV) heterozygous group of patients at codon 129. The absolute levels of S100b (p < 0.05), NSE and tau protein increased in the last stage of disease. High levels of tau protein, NSE and S100b were associated with shorter survival times (p < 0.01). Sixty-six sCJD patients underwent repeated LP. These sCJD patients were younger, had longer disease durations and were more frequently MV at codon 129 (p < 0.001) than the whole group. 14-3-3 sensitivity increased from 64% to 82% in the second LP (p = 0.025) and 88% sCJD patients had at least one positive result. Conclusions: Sensitivity and absolute levels of CJD markers increased with disease progression and were modulated by the codon 129 genotype. Early negative results should be inter-preted with caution, especially in young patients or those who are MV at codon 129. CSF analysis in patients with sporadic CJD and other transmissible spongiform encephalopathieshttp://repub.eur.nl/pub/36828/
Thu, 01 Feb 2007 00:00:01 GMT<div>A. Green</div><div>P. Sanchez-Juan</div><div>A. Ladogana</div><div>N. Cuadrado-Corrales</div><div>R. Sánchez-Valle</div><div>E. Mitrová</div><div>K. Stoeck</div><div>T. Sklaviadis</div><div>J. Kulczycki</div><div>U. Heinemann</div><div>K. Hess</div><div>D. Slivarichová</div><div>A. Saiz</div><div>M. Calero</div><div>V. Mellina</div><div>R.S.G. Knight</div><div>P. Tikka-Kleemola</div><div>I. Zerr</div>
Patients with suspected Creutzfeldt-Jakob disease (CJD) often have routine cerebrospinal fluid (CSF) analysis performed to exclude treatable inflammatory conditions; however, little information is available about the range of results obtained for CSF tests in patients with sporadic CJD and other transmissible spongiform encephalopathies (TSE). Data from 450 patients with sporadic CJD and 47 patients with other TSEs were collected as part of an EC-supported multinational study. Raised white cell counts of >5 cells/μl were found in three of 298 patients with sporadic CJD, with two cell counts of 7 cells/μl and one of 20 cells/μl. Total protein concentrations of >0.9 g/l were found in five of 438 patients with sporadic CJD, although none had a concentration of >1 g/l. CSF oligoclonal IgG was detected in eight of 182 sporadic CJD patients. Of the patients with other TSEs, six had elevated cell counts ranging from 6 to 14 cells/μl but none had total protein concentrations of >0.9 g/l and one patient had detectable oligoclonal IgG. None of the patients with sporadic CJD or other TSEs had abnormalities in all three tests. Human transmissible spongiform encephalopathies in eleven countries: Diagnostic pattern across time, 1993-2002http://repub.eur.nl/pub/71207/
Fri, 10 Nov 2006 00:00:01 GMT<div>J. de Pedro-Cuesta</div><div>M. Glatzel</div><div>J. Almazán</div><div>K. Stoeck</div><div>V. Mellina</div><div>M. Puopolo</div><div>M. Pocchiari</div><div>I. Zerr</div><div>H.A. Kretszchmar</div><div>J-P. Brandel</div><div>N. Delasnerie-Laupretre</div><div>A. Alperovitch</div><div>C.M. van Duijn</div><div>P. Sanchez-Juan</div><div>S.J. Collins</div><div>V. Lewis</div><div>G. Jansen</div><div>M.B. Coulthart</div><div>E. Gelpi</div><div>H. Budka</div><div>E. Mitrová</div>
Background: The objective of this study was to describe the diagnostic panorama of human transmissible spongiform encephalopathies across 11 countries. Methods: From data collected for surveillance purposes, we describe annual proportions of deaths due to different human transmissible spongiform encephalopathies in eleven EUROCJD-consortium countries over the period 1993-2002, as well as variations in the use of diagnostic tests. Using logistic models we quantified international differences and changes across time. Results: In general, pre-mortem use of diagnostic investigations increased with time. International differences in pathological confirmation of sporadic Creutzfeldt-Jakob disease, stable over time, were evident. Compared to their counterparts, some countries displayed remarkable patterns, such as: 1) the high proportion, increasing with time, of variant Creutzfeldt-Jakob disease in the United Kingdom, (OR 607.99 95%CI 84.72-4363.40), and France (OR 18.35, 95%CI 2.20-152.83); 2) high, decreasing proportions of iatrogenic Creutzfeldt-Jakob disease in France, (OR 5.81 95%CI 4.09-8.24), and the United Kingdom, (OR 1.54 95%CI 1.03-2.30); and, 3) high and stable ratios of genetic forms in Slovakia (OR 21.82 95%CI 12.42-38.33) and Italy (OR 2.12 95%CI 1.69-2.68). Conclusion: Considerable international variation in aetiological subtypes of human transmissible spongiform encephalopathies was evident over the observation period. With the exception of variant Creutzfeldt-Jakob disease and iatrogenic Creutzfeldt-Jakob disease in France and the United Kingdom, these differences persisted across time.Predictors of survival in sporadic Creutzfeldt-Jakob disease and other human transmissible spongiform encephalopathies.http://repub.eur.nl/pub/13499/
Fri, 01 Oct 2004 00:00:01 GMT<div>M. Pocchiari</div><div>M. Puopolo</div><div>E.A. Croes</div><div>H. Budka</div><div>E. Gelpi</div><div>S.J. Collins</div><div>V. Lewis</div><div>T. Sutcliffe</div><div>A. Guilivi</div><div>N. Delasnerie-Laupretre</div><div>J-P. Brandel</div><div>A. Alperovitch</div><div>I. Zerr</div><div>S. Poser</div><div>H.A. Kretzschmar</div><div>A. Ladogana</div><div>I. Rietvald</div><div>E. Mitrová</div><div>P. Martinez-Martin</div><div>J. de Pedro-Cuesta</div><div>M. Glatzel</div><div>S. Cooper</div><div>J. Mackenzie</div><div>C.M. van Duijn</div><div>R.G. Will</div><div>A. Aguzzi</div>
A collaborative study of human transmissible spongiform encephalopathies has been carried out from 1993 to 2000 and includes data from 10 national registries, the majority in Western Europe. In this study, we present analyses of predictors of survival in sporadic (n = 2304), iatrogenic (n = 106) and variant Creutzfeldt-Jakob disease (n = 86) and in cases associated with mutations of the prion protein gene (n = 278), including Gerstmann-Straussler-Scheinker syndrome (n = 24) and fatal familial insomnia (n = 41). Overall survival for each disease type was assessed by the Kaplan-Meier method and the multivariate analyses by the Cox proportional hazards model. In sporadic disease, longer survival was correlated with younger age at onset of illness, female gender, codon 129 heterozygosity, presence of CSF 14-3-3 protein and type 2a prion protein type. The ability to predict survival based on patient covariates is important for diagnosis and counselling, and the characterization of the survival distributions, in the absence of therapy, will be an important starting point for the assessment of potential therapeutic agents in the future.Codon 129 prion protein genotype and sporadic Creutzfeldt-Jakob diseasehttp://repub.eur.nl/pub/5872/
Fri, 01 Jan 1999 00:00:01 GMT<div>A. Alperovitch</div><div>I. Zerr</div><div>M. Pocchiari</div><div>E. Mitrová</div><div>J. de Pedro-Cuesta</div><div>I. Hegyi</div><div>S.J. Collins</div><div>H. Kretzschmar</div><div>C.M. van Duijn</div><div>R.G. Will</div>